ATF4

ATF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1CI6
Identifiers
Aliases	ATF4, CREB-2, CREB2, TAXREB67, TXREB, activating transcription factor 4
External IDs	MGI: 88096 HomoloGene: 1266 GeneCards: ATF4
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q13.1 Start 39,519,695 bp[1] End 39,522,685 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 E1|15 37.85 cM Start 80,255,184 bp[2] End 80,257,541 bp[2]
Gene ontology Molecular function • RNA polymerase II transcription factor binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcription factor activity, RNA polymerase II transcription factor binding • leucine zipper domain binding • protein binding • protein heterodimerization activity • transcription regulatory region DNA binding • transcription factor activity, sequence-specific DNA binding • DNA binding • core promoter sequence-specific DNA binding • sequence-specific DNA binding • protein kinase binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding • protein C-terminus binding • transcription factor binding • RNA polymerase II distal enhancer sequence-specific DNA binding Cellular component • Lewy body core • nuclear periphery • membrane • transcription factor complex • plasma membrane • dendrite membrane • nucleoplasm • microtubule organizing center • neuron projection • cytoskeleton • CHOP-ATF4 complex • ATF4-CREB1 transcription factor complex • cytoplasm • cell nucleus • ATF1-ATF4 transcription factor complex • centrosome • macromolecular complex Biological process • gamma-aminobutyric acid signaling pathway • positive regulation of transcription from RNA polymerase II promoter in response to arsenic-containing substance • cellular response to glucose starvation • negative regulation of translational initiation in response to stress • rhythmic process • cellular response to UV • positive regulation of transcription from RNA polymerase II promoter in response to stress • regulation of transcription from RNA polymerase II promoter • cellular amino acid metabolic process • transcription from RNA polymerase II promoter • transcription, DNA-templated • response to manganese-induced endoplasmic reticulum stress • positive regulation of gene expression • circadian rhythm • negative regulation of potassium ion transport • positive regulation of apoptotic process • positive regulation of vascular endothelial growth factor production • positive regulation of transcription from RNA polymerase I promoter • positive regulation of transcription from RNA polymerase II promoter • positive regulation of neuron apoptotic process • positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress • intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress • positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress • gluconeogenesis • PERK-mediated unfolded protein response • regulation of transcription, DNA-templated • negative regulation of oxidative stress-induced neuron death • cellular response to amino acid starvation • circadian regulation of gene expression • positive regulation of transcription, DNA-templated • mRNA transcription from RNA polymerase II promoter • response to endoplasmic reticulum stress • cellular response to dopamine • response to toxic substance • neuron differentiation • cellular response to oxygen-glucose deprivation • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	468	11911
Ensembl	ENSG00000128272	ENSMUSG00000042406
UniProt	P18848 Q96AQ3	Q06507
RefSeq (mRNA)	NM_182810 NM_001675	NM_001287180 NM_009716
RefSeq (protein)	NP_001666 NP_877962 NP_001666.2 NP_877962.1	NP_001274109 NP_033846
Location (UCSC)	Chr 22: 39.52 – 39.52 Mb	Chr 15: 80.26 – 80.26 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a protein that in humans is encoded by the ATF4 gene.^[5][6]

Function

This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein–protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA-binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromosome at q28 in a region containing a large inverted duplication.^[7]

ATF4 transcription factor is also known to play role in osteoblast differentiation along with RUNX2 and osterix.^[8] Terminal osteoblast differentiation, represented by matrix mineralization, is significantly inhibited by the inactivation of JNK. JNK inactivation downregulates expression of ATF-4 and, subsequently, matrix mineralization.^[9] IMPACT protein regulates ATF4 in C. elegans to promote lifespan.^[10]

Translation

The translation of ATF4 is dependent on upstream open reading frames located in the 5'UTR.^[11] The location of the second uORF, aptly named uORF2, overlaps with the ATF4 open-reading frame. During normal conditions, the uORF1 is translated, and then translation of uORF2 occurs only after eIF2-TC has been reacquired. Translation of the uORF2 requires that the ribosomes pass by the ATF4 ORF, whose start codon is located within uORF2. This leads to its repression. However, during stress conditions, the 40S ribosome will bypass uORF2 because of a decrease in concentration of eIF2-TC, which means the ribosome does not acquire one in time to translate uORF2. Instead ATF4 is translated.^[11]

See also

• Activating transcription factor

References

Further reading

External links

• ATF4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human ATF4 genome location and ATF4 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.